The investigators propose to study new types of synthetic water soluble polymer systems-for the treatment of colon disease. These systems will be based on the concept of binding of polymeric carriers containing carbohydrate moieties complementary of colonic mucosal lectins and on the concept of site-specific release of drug N(2-aminosalicylic acid) by the degrading action of microbial enzymes present in the colon on the polymeric carriers. The aim is to design copolymer-drug conjugates which will increase the effectiveness of drugs given orally. The preliminary studies demonstrated that: 1) New synthetic routes are available to synthesize N(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing high amounts of both the bioadhesive moiety (fucosylamine) and 5-aminosalicylic acid (5-ASA). 2) HPMA copolymers containing fucosylamine bind specifically to the colonic mucosa of guinea pigs in vitro and in vivo. The higher the content of fucosylamine, the higher the binding. The binding can be inhibited by unbound fucose indicating the presence of a specific lectin in the colonic mucosa. 3) Incorporation of 5-ASA into fucose containing copolymers further increases the binding to the colon in vitro and in vivo. 4) 5-ASA is released from the bioadhesive HPMA copolymers by Streptococcus faecium and by cecal rat cell free extract in vitro. In this application, bioadhesive HPMA copolymers containing high amounts of fucose and 5-ASA will be synthesized. The fucose binding lectin will be isolated from the guinea pig colon and characterized. Structural factors responsible for the association of HPMA copolymers with the lectin will be determined and the structure of bioadhesive HPMA copolymers will be optimized for the treatment of ulcerative colitis in guinea pigs. Based on pharmacokinetic studies and on the in vivo evaluation of the therapeutic efficacy, criteria will be established for the design of a new oral 5-ASA delivery system for clinical use. Experiments will be performed with human fecalase and cadaver colonic tissue to establish the correlation between animal and human tissue. The results of proposed studies will provide a new therapeutic method for the treatment of ulcerative colitis. Moreover, they will be of importance for the development of other colon-specific drug delivery systems.